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Aging affects the structure and functions of all organs and systems in the organism. In the elderly, significant changes in hormonal levels are observed. These translate to a predisposition for chronic diseases, including cardiovascular, neurodegenerative, and metabolic disorders. Therefore, tremendous scientific effort is focused on investigating molecular mechanisms and drugs with the potential to reduce hormonal changes in old age and their impact. Sirtuin 1 (SIRT1), a member of the sirtuin family of deacetylases, has been extensively studied as a regulator of multiple pathways related to antioxidant properties, optimal immune response, and metabolism. SIRT1 plays a key role in regulating various hormonal pathways and maintaining homeostasis. In the present study, we review the interplay between SIRT1 and hormonal regulations, including the endocrine role of the hypothalamic–pituitary–thyroid, –adrenal, –gonadal, and –liver axes, of other endocrine glands, and of non-endocrine tissues in the aging organism. The application of natural SIRT1 activators, such as resveratrol, curcumin, paeonol, and Buyang Huanwu Decoction, for the treatment of aging and senescence is discussed. SIRT1 activators improve mitochondrial function, reduce oxidative stress, and promote longevity, but their clinical application is limited by low bioavailability and poor permeability across biological barriers. For this reason, advanced delivery strategies are being considered, including nose-to-brain drug delivery and nanotechnology-based formulations. [ABSTRACT FROM AUTHOR]

Obesity, a global pandemic, poses a major threat to healthcare systems worldwide. Adipose tissue, the energy-storing organ during excessive energy intake, functions as a thermoregulator, interacting with other tissues to regulate systemic metabolism. Specifically, brown adipose tissue (BAT) is positively associated with an increased resistance to obesity, due to its thermogenic function in the presence of uncoupled protein 1 (UCP1). Recently, studies on climate change and the influence of environmental pollutants on energy homeostasis and obesity have drawn increasing attention. The reciprocal relationship between increasing adiposity and increasing temperatures results in reduced adaptive thermogenesis, decreased physical activity, and increased carbon footprint production. In addition, the impact of climate change makes obese individuals more prone to developing type 2 diabetes mellitus (T2DM). An impaired response to heat stress, compromised vasodilation, and sweating increase the risk of diabetes-related comorbidities. This comprehensive review provides information about the effects of climate change on obesity and adipose tissue, the risk of T2DM development, and insights into the environmental pollutants causing adipose tissue dysfunction and obesity. The effects of altered dietary patterns on adiposity and adaptation strategies to mitigate the detrimental effects of climate change are also discussed. [ABSTRACT FROM AUTHOR]

This manuscript explores the intricate role of acetylcholine-activated inward rectifier potassium (KACh) channels in the pathogenesis of atrial fibrillation (AF), a common cardiac arrhythmia. It delves into the molecular and cellular mechanisms that underpin AF, emphasizing the vital function of KACh channels in modulating the atrial action potential and facilitating arrhythmogenic conditions. This study underscores the dual nature of KACh activation and its genetic regulation, revealing that specific variations in potassium channel genes, such as Kir3.4 and K2P3.1, significantly influence the electrophysiological remodeling associated with AF. Furthermore, this manuscript identifies the crucial role of the KACh-mediated current, IKACh, in sustaining arrhythmia through facilitating shorter re-entry circuits and stabilizing the re-entrant circuits, particularly in response to vagal nerve stimulation. Experimental findings from animal models, which could not induce AF in the absence of muscarinic activation, highlight the dependency of AF induction on KACh channel activity. This is complemented by discussions on therapeutic interventions, where KACh channel blockers have shown promise in AF management. Additionally, this study discusses the broader implications of KACh channel behavior, including its ubiquitous presence across different cardiac regions and species, contributing to a comprehensive understanding of AF dynamics. The implications of these findings are profound, suggesting that targeting KACh channels might offer new therapeutic avenues for AF treatment, particularly in cases resistant to conventional approaches. By integrating genetic, cellular, and pharmacological perspectives, this manuscript offers a holistic view of the potential mechanisms and therapeutic targets in AF, making a significant contribution to the field of cardiac arrhythmia research. [ABSTRACT FROM AUTHOR]

Oxygen therapy provides an important treatment for preterm and low-birth-weight neonates, however, it has been shown that prolonged exposure to high levels of oxygen (hyperoxia) is one of the factors contributing to the development of bronchopulmonary dysplasia (BPD) by inducing lung injury and airway hyperreactivity. There is no effective therapy against the adverse effects of hyperoxia. Therefore, this study was undertaken to test the hypothesis that natural phytoalexin resveratrol will overcome hyperoxia-induced airway hyperreactivity, oxidative stress, and lung inflammation. Newborn rats were exposed to hyperoxia (fraction of inspired oxygen - FiO2>95 % O2) or ambient air (AA) for seven days. Resveratrol was supplemented either in vivo (30 mg·kg-1·day-1) by intraperitoneal administration or in vitro to the tracheal preparations in an organ bath (100 µM). Contractile and relaxant responses were studied in tracheal smooth muscle (TSM) using the in vitro organ bath system. To explain the involvement of nitric oxide in the mechanisms of the protective effect of resveratrol against hyperoxia, a nitric oxide synthase inhibitor - Nω-nitro-L-arginine methyl ester (L-NAME), was administered in some sets of experiments. The superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and the tumor necrosis factor-alpha (TNF-α) and interleukin-1γ (IL-1γ) levels in the lungs were determined. Resveratrol significantly reduced contraction and restored the impaired relaxation of hyperoxia-exposed TSM (p<0.001). L-NAME reduced the inhibitory effect of resveratrol on TSM contractility, as well as its promotion relaxant effect (p<0.01). Resveratrol preserved the SOD and GPx activities and decreased the expression of TNF-α and IL-1γ in hyperoxic animals. The findings of this study demonstrate the protective effect of resveratrol against hyperoxia-induced airway hyperreactivity and lung damage and suggest that resveratrol might serve as a therapy to prevent the adverse effects of neonatal hyperoxia. [ABSTRACT FROM AUTHOR]

Background: The study aimed to identify transcripts of specific ion channels in rat ventricular cardiomyocytes and determine their potential role in the regulation of ionic currents in response to mechanical stimulation. The gene expression levels of various ion channels in freshly isolated rat ventricular cardiomyocytes were investigated using the RNA-seq technique. We also measured changes in current through CaV1.2 channels under cell stretching using the whole-cell patch-clamp method. Results: Among channels that showed mechanosensitivity, significant amounts of TRPM7, TRPC1, and TRPM4 transcripts were found. We suppose that the recorded L-type Ca2+ current is probably expressed through CaV1.2. Furthermore, stretching cells by 6, 8, and 10 μm, which increases ISAC through the TRPM7, TRPC1, and TRPM4 channels, also decreased ICa,L through the CaV1.2 channels in K+in/K+out, Cs+in/K+out, K+in/Cs+out, and Cs+in/Cs+out solutions. The application of a nonspecific ISAC blocker, Gd3+, during cell stretching eliminated ISAC through nonselective cation channels and ICa,L through CaV1.2 channels. Since the response to Gd3+ was maintained in Cs+in/Cs+out solutions, we suggest that voltage-gated CaV1.2 channels in the ventricular myocytes of adult rats also exhibit mechanosensitive properties. Conclusions: Our findings suggest that TRPM7, TRPC1, and TRPM4 channels represent stretch-activated nonselective cation channels in rat ventricular myocytes. Probably the CaV1.2 channels in these cells exhibit mechanosensitive properties. Our results provide insight into the molecular mechanisms underlying stretch-induced responses in rat ventricular myocytes, which may have implications for understanding cardiac physiology and pathophysiology. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) and associated oxidative stress are the main contributors to pathophysiological changes following myocardial infarction (MI), which is the principal cause of death from cardiovascular disease. The glutathione (GSH)/glutathione peroxidase (GPx) system appears to be the main and most active cardiac antioxidant mechanism. Hence, enhancement of the myocardial GSH system might have protective effects in the setting of MI. It follows that by increasing antioxidant capacity, the heart will be able to reduce the damage associated with MI and even prevent/weaken the occurrence of oxidative stress, which is highly ranked among the factors responsible for the occurrence of acute MI. For these reasons, the primary goal of future investigations should be to address the effects of different antioxidative compounds and especially cysteine derivatives like N-acetyl cysteine (NAC) and L-2-oxothiazolidine-4-carboxylic acid (OTC) as precursors responsible for the enhancement of the GSH-related antioxidant system's capacity. It is assumed that this will lay down the basis for elucidation of the mechanisms throughout which applicable doses of OTC will manifest a potentially positive impact in the reduction of adverse effects of acute MI. The inclusion of OTC in the models for prediction of the distribution of oxygen in infarcted animal hearts can help to upgrade existing computational models. Such a model would be based on computational geometries of the heart, but the inclusion of biochemical redox features in addition to angiogenic therapy, despite improvement of the post-infarcted oxygenated outcome could enhance the accuracy of the predictive values of oxygenation. [ABSTRACT FROM AUTHOR]